Sarcoma RTP

1. Synovial sarcoma advanced- MAGE A4 T cell re-engineered therapy FDA approval 

2. types of sarcoma in which IO can be useful:

Angiosarcoma

undifferentiated pleomorphic sarcoma

3. Types of chemo sensitive sarcoma

- Ewing's, osteosarcoma, rhabdomyosarcoma, myxoid or round cell liposarcoma( very sensitive to chemo)

4.  Liposarcoma 15-20%, another 15-20% leiomyosarcoma

5. 5 different types of liposarcoma:

- well differentiated--> indolent, surgery is the main Rx

-dedifferentiated--> aggressive, not sensitive to radiation, doxorubicin can be used +/- ifosfamide. Low ORR 20%, not much to be gained with 2 agents, pFS 2-4 m, 2nd line eribulin or trabectedin per FDA, although gem taxotere can be used 1L or 2L.

-myxoid or round cell--> chemo sensitive, T cell therapy is effective, very sensitive to radiation as well

6. What's with MDM2: Even in cells that have wild type P53, MDM2 amplification can inactivate the protective effects of p53.

90% of liposarcoma, it’s a universally MDM2 amplified in all these liposarcomas, and p53 is rarely mutated.

 In lung cancer nearly 10% of lung cancer has MDM2 amplification, they have p53 wild-type. Head and neck cancers, bladder, everything is 10% or so, have high levels of MDM2 amplification and wild-type p53.

prostate 7%, breast 5%, GBM a whopping 25% have MDM2 amplifications. 

7. Brigimadlin now of interest in gall bladder ( MDM2 inhibitor) cancers https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.487